The overall goal of this research is to identify specific populations of enteric neurons that are activated by the gut hormones Cholecystokinin (CCK), bombesin and leptin, and to determine the role of CCK receptors, vagus nerve and capsaicin-sensitive neurons in this activation. CCK and nutrients (release CCK (glucose and oleate [fat]), bombesin and leptin (both have synergistic action with CCK) participate in various crucial gastrointestinal functions such as motility or secretion. Also, they play a significant role in the control of food intakeI obesity through evoking many responses such as reduction of food intake and inhibition of gastric emptying. Thus, our first goal is to determine if each of these peptides activate myenteric and sub-mucosal neurons in the rat duodenum, jejunum, ileum, cecum, colon and rectum. The enteric plexuses have numerous neuronal subpopulations, with various shapes and functions. Our second goal is to identify what specific enteric neuronal subpopulations are activated by those stimuli. CCK has two receptors, CCK-A and CCK-B. These receptors mediate different functions in the gastrointestinal tract. Also, there is clear evidence that CCK is either released by nutrients such as fat or glucose when they enter to the small intestine, or act synergistically with bombesin and leptin. Our third goat is to determine the role of each receptor in activation of the enteric neurons by either nutrient, which release CCK or each of the peptides alone or in combination with CCK. The neural control of the gastrointestinal tract is mainly intrinsic. However, the vagus nerve contains the major extrinsic neural supply to the gastrointestinal tract. We suspect that the vagus nerve or the small sensory neurons may have a role in activation of enteric neurons by these peptides and nutrients. Thus, our fourth goal is to determine the role of the vagus nerve and the small sensory neurons in activation ,of the enteric plexuses by the previous peptides or nutrients. We will utilize detection of nuclear Fos as a marker for neuronal activation, and immunoreactivity of five phenotypic markers, NOS, Calbindin, Calretinin, Neurofilament-M and neurokinin-1 receptor.